As a first prior art related to the present invention, a technology can be listed such that after a substance (hereinafter referred to as “probe substance”) serving as a probe to detect a target substance is immobilized beforehand to a solid-phase surface such as a metal film, a base plate of a synthetic resin or glass or beads, a specific interaction between substances is utilized to capture and recover the target substance to analyze its structure by mass spectrometry. Use of this technology allows finding a substance interacting with the above-mentioned probe substance.
In the above-mentioned technology, a substance called a linker, spacer or tag can be inserted between the probe substance and a solid-phase surface and labeled to try to adjust a bonding force between the probe substance and the solid-phase surface, resolve steric hindrance and improve the utilization efficiency of the reaction space. Such technology becomes an important elemental technology such as a surface plasmon resonance sensor and a microarray chip with an assembly of DNA and/or protein in a biosensor technology and immunoprecipitation technique.
In general, an “avidin-biotin binding system” is widely used to immobilize the probe substance to the solid-phase surface. Avidin is a glycoprotein to specifically strongly bind to biotin. Because avidin has very high affinity to biotin, it is used to immobilize a biotinylated DNA, peptide and protein.
For example, a solid-phase surface is precoated with avidin such as streptavidin to firmly bind (immobilization) to a biotinylated probe substance. In other cases, the avidin-biotin binding system is widely used in a field of the immunological measurement such as enzyme immunoassay (EIA) and tissue staining.
Some of the prior art using the “avidin-biotin binding system” are listed herein. First, Patent Document 1 discloses a technology, in which after a biotinylated antigen or antibody is bound to avidin or streptavidin immobilized, it is contacted with a solution of a labeling compound to specifically bind to the antibody or antigen in a sample to detect “a labeled antigen-antibody complex.” Patent Document 2 also discloses a technology, in which a solution containing a biotinylated probe DNA is spotted onto a solid-phased film, in which an avidin molecule is immobilized as a monolayer, yielding a DNA microarray.
Next, an interactive analysis technology using an “epitope tag peptide” is listed as a second prior technology related to the present invention.
For example, Nonpatent Document 1 discloses a technology below. First, while a recombinant protein fused with an epitope tag peptide is expressed, beads with an immobilized antibody specifically recognizing the epitope tag peptide are mixed with a cell extract. A target protein in the cell extract is trapped via the recombinant protein and then the beads are thoroughly washed, to which an excess amount of the epitope tag peptide is added to replace the protein trapped on the beads with the added peptide to elute the target protein (and a recombinant protein fused) into a liquid phase.
That is, Nonpatent Document 1 discloses an interactive analysis technology using a composition of a “fused protein-peptide tag.” This fused protein-peptide tag is one with a series of amino acid sequences between homologous species, so that it can be synthesized using the genetic translation system in an organism.
Patent Document 1: Japanese Published Unexamined Patent Application No. Hei-09-133683
Patent Document 2: Japanese Published Unexamined Patent Application No. 2002-153272
Nonpatent Document 1: Experimental Medicine, Supplementary Volume, Post-Genome Era Experimental Course 2, “Analysis of proteome/frontier technology in protein expression and its functional analysis and study on genomic medicine and drug discovery,” Yodosha, Toshiaki Isobe and Nobuhiro Takahashi ed., p. 166-174.